Acute regulation of peripheral blood flow and long-term microvascular remodeling play central roles in vascular biology because they are essential mechanisms enabling normal vascular adaptation in exercise and would healing, as well as compensation for stroke, myocardial infarction, and trauma. Despite intensive effort that has been focused on possible therapeutic benefits of magnetic fields in tissue survival and recovery following ischemic insult or trauma, little is known of the response of intact blood vessel networks to application of magnetic fields in vivo. This study is designed to test the central hypotheses that static magnetic fields induce arteriolar vasodilation in intact tissues and enhance the growth of microvascular networks via the production of stress-mediated cytokines. The long-term objective is to advance understanding and optimize the design of therapeutic magnetic fields based on the molecular mechanisms mediating acute vasoactivity and chronic remodeling of complete microvascular networks in vivo. The specific aims of the research are to determine the sites and time sequence of arteriolar vasodilation and blood flow rate in intact arteriolar networks of skeletal muscle in vivo, with and without neural blockade, inhibition of Ca2+-ATPase, and inhibition of nitric oxide synthase; to establish the efficacy of magnetic field application on recovery of blood flow and reduction of tissue injury after acute ischemia/reperfusion episodes; to establish the role of magnetic fields in arteriolar remodeling and capillary angiogenesis in skeletal muscle in vivo, both under normal conditions and after chronic or acute vascular obstruction; to determine whether fibroblast recruitment and differentiation or smooth muscle proliferation is mediated by cytokine expression in the microvascular network during chronic application of magnetic fields using in situ hybridization and blocking antibodies to PDGF and TGF-beta in a mesenteric widow assay; and to use a mathematical computer simulation of the microvascular network of spinotrapezius muscle to test the roles of altered wall stresses and propagated vasodilation in the acute arteriolar response and long-term arteriolar pattern formation during magnetic field application in vivo. Not only have these methods provided the first demonstration of acute arteriolar vasodilation in a static magnetic field, but the techniques represent an innovative experimental platform that opens the way for in vivo study of molecular regulation of microvascular network adaptation during magnetic field application, a subject of vast therapeutic importance.